Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2
Nuclear hormone receptors, including RXR and PPARγ, represent novel therapeutic targets in melanoma. We have previously shown that the DRO subline of the amelanotic melanoma A375 responds to rexinoid and thiazolidinedione (TZD) treatment in vitro and in vivo. We performed microarray analysis of A375...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2010/729876 |
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| _version_ | 1832564655306833920 |
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| author | Joshua P. Klopper Vibha Sharma Reid Bissonnette Bryan R. Haugen |
| author_facet | Joshua P. Klopper Vibha Sharma Reid Bissonnette Bryan R. Haugen |
| author_sort | Joshua P. Klopper |
| collection | DOAJ |
| description | Nuclear hormone receptors, including RXR and PPARγ, represent novel therapeutic targets in melanoma. We have previously shown that the DRO subline of the amelanotic melanoma A375 responds to rexinoid and thiazolidinedione (TZD) treatment in vitro and in vivo. We performed microarray analysis of A375(DRO) after TZD and combination rexinoid/TZD treatment in which the calcium binding protein S100A2 had increased expression after rexinoid or TZD treatment and a synergistic increase to combination treatment. Increased S100A2 expression is dependent on an intact PPARγ receptor, but it is not sufficient to mediate the antiproliferative effects of rexinoid/TZD treatment. Over expression of S100A2 enhanced the effect of rexinoid and TZD treatment while inhibition of S100A2 expression attenuated the response to rexinoid/TZD treatment, suggesting that S100A2 is necessary for optimal response to RXR and PPARγ activation by respective ligands. In summary, we have identified potential downstream mediators of rexinoid and TZD treatment in a poorly differentiated melanoma and found that alterations in S100A2 expression affect RXR and PPARγ signaling in A375(DRO) cells. These studies provide insight into potential mechanisms of tumor response or resistance to these novel therapies. |
| format | Article |
| id | doaj-art-006655c7cc384c58b5c8e2c096141416 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-006655c7cc384c58b5c8e2c0961414162025-02-03T01:10:31ZengWileyPPAR Research1687-47571687-47652010-01-01201010.1155/2010/729876729876Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2Joshua P. Klopper0Vibha Sharma1Reid Bissonnette2Bryan R. Haugen3Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USADivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USADepartment of Molecular Oncology, Ligand Pharmaceuticals, San Diego, CA 92121, USADivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USANuclear hormone receptors, including RXR and PPARγ, represent novel therapeutic targets in melanoma. We have previously shown that the DRO subline of the amelanotic melanoma A375 responds to rexinoid and thiazolidinedione (TZD) treatment in vitro and in vivo. We performed microarray analysis of A375(DRO) after TZD and combination rexinoid/TZD treatment in which the calcium binding protein S100A2 had increased expression after rexinoid or TZD treatment and a synergistic increase to combination treatment. Increased S100A2 expression is dependent on an intact PPARγ receptor, but it is not sufficient to mediate the antiproliferative effects of rexinoid/TZD treatment. Over expression of S100A2 enhanced the effect of rexinoid and TZD treatment while inhibition of S100A2 expression attenuated the response to rexinoid/TZD treatment, suggesting that S100A2 is necessary for optimal response to RXR and PPARγ activation by respective ligands. In summary, we have identified potential downstream mediators of rexinoid and TZD treatment in a poorly differentiated melanoma and found that alterations in S100A2 expression affect RXR and PPARγ signaling in A375(DRO) cells. These studies provide insight into potential mechanisms of tumor response or resistance to these novel therapies.http://dx.doi.org/10.1155/2010/729876 |
| spellingShingle | Joshua P. Klopper Vibha Sharma Reid Bissonnette Bryan R. Haugen Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2 PPAR Research |
| title | Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2 |
| title_full | Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2 |
| title_fullStr | Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2 |
| title_full_unstemmed | Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2 |
| title_short | Combination PPARγ and RXR Agonist Treatment in Melanoma Cells: Functional Importance of S100A2 |
| title_sort | combination pparγ and rxr agonist treatment in melanoma cells functional importance of s100a2 |
| url | http://dx.doi.org/10.1155/2010/729876 |
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